1. Name Of The Medicinal Product
Metoclopramide Hydrochloride 5mg/5ml Oral Solution
2. Qualitative And Quantitative Composition
Metoclopramide Hydrochloride BP 5mg/5ml
3. Pharmaceutical Form
Oral Solution
4. Clinical Particulars
4.1 Therapeutic Indications
1. Symptomatic relief of gastro-duodenal dysfunction, including: dyspepsia, flatulence, heartburn, pain, regurgitation of bile and sickness.
2. Nausea and vomiting
3. Migraine
4. Restoration of normal gastric emptying and motility in post operative conditions.
5. In diagnostic procedures such as radiology and duodenal intubation. Speeds up passage of a barium meal by decrease of gastric emptying time, dilation of duodenal bulb and co-ordination of peristalsis.
6. In young adults and children, Metoclopramide Hydrochloride must be restricted to the following uses:-
- severe, intractable vomiting, of which the cause is known.
- vomiting caused by radiotherapy and/or intolerance to cytotoxic agents.
- aid to gastro-intestinal intubation
- pre-medication prior to surgical procedures.
4.2 Posology And Method Of Administration
For oral administration only.
Dosage recommendations given should be strictly followed to avoid dystonic side effects. Total daily dosage of Metoclopramide Hydrochloride Oral Solution should not exceed 0.5mg/Kg of body weight under normal circumstances. Dosage should be at reduced levels in patients with significant renal or hepatic impairment.
FOR MEDICAL INDICATIONS
Adults of 20 years and older:
10mg three times daily. If weigh below 60Kg see later.
Elderly
As for adults, adhere to dosage recommendations to avoid adverse reactions, if on prolonged therapy, review regularly.
Young adults and children:
Only use Metoclopramide Hydrochloride Oral Solution after examination to avoid masking an underlying disorder, such as cerebral irritation.
Primary consideration must be given to body weight and treatment should be initiated at the lower dosage indicated.
Young Adults (15 - 19 years old):
Weight 60Kg and over - 10mg three times daily.
Weight 30Kg - 59Kg, 5mg three times daily
Children
9 - 14 years old, weight 30Kg and over, 5mg, three times daily.
5 - 9 years old, weight 20 - 29 Kg, 2.5mg three times daily
3 - 5 years old, weight 15 - 19Kg, 2mg two to three times daily
1 - 3 years old, weight 10 -14Kg, 1mg, two to three times daily
Under 1 year, weight up to 10Kg, 1mg, twice daily
Accurate dosage is facilitated by the use of a 30ml pack with a 1ml dropper
FOR DIAGNOSTIC INDICATIONS
A single dose of Metoclopramide Hydrochloride Oral Solution, 5 to 10 minutes prior to examination. Subject to body weight factors, recommended doses are :-
Adults - 20 years and older
10 - 20mg
Young adults
15 - 19 years old, 10mg
9 - 14 years old, 5mg
5 - 9 years old, 2.5mg
3 - 5 years old, 2mg
Under 3 years old, 1mg
4.3 Contraindications
Hypersensitivity to metoclopramide hydrochloride.
Patients hypersensitive to procaine and procainamide may show cross-sensitivity.
Hypersensitivity to hydroxybenzoates.
Epilepsy - severity and frequency of seizures may be increased.
Metoclopramide should not be used during the first three to four days following operations such as pyloroplasty or gut anastomosis as vigorous muscular contractions may not help healing
Gastro-intestinal haemorrhage, mechanical obstruction or perforation; stimulation of gastro-intestinal motility may aggravate condition.
Phaeochromocytoma - may cause crisis.
4.4 Special Warnings And Precautions For Use
If, despite treatment, vomiting persists, the patient must be re-assessed to exclude the possibility of an underlying disorder, i.e. cerebral irritation.
Risk-benefit should be considered in patients with:-
- Liver disease, due to loss of conjugation
- Parkinson's disease, as symptoms may be exacerbated.
- Severe or chronic renal failure, as the risk of extrapyramidal effects may be increased; dosage reduction is recommended.
Avoid alcohol.
Neuroleptic malignant syndrome has been reported with metoclopramide in combination with neuroleptics as well as with metoclopramide monotherapy (See section 4.8 Undesirable effects).
Care should be exercised when using metoclopramide in patients with a history of atopy (including asthma) or porphyria
Excipient Warnings
This product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Methyl and propyl hydroxybenzoates are contained in this product which may cause allergic reactions (possibly delayed).
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Note that combinations containing any of the following drugs, dependent upon the quantity, may also interact.
1. Alcohol: Concurrent use may increase the central nervous system (CNS) depressant effects of either alcohol or metoclopramide; concurrent use may also accelerate gastric emptying of alcohol and thus may promote the rate and extent of absorption from the small intestine.
2. Antimuscarinics or other drugs with anti-muscarininc activity or opioid analgesic containing medicines: Concurrent use may antagonise the effects of metoclopramide on gastro-intestinal motility.
3. Apomorphine: Prior administration of metoclopramide may decrease the emetic response to apomorphine; also, concurrent use may potentiate the CNS depressant effects of either apomorphine or metoclopramide.
4. Bromocriptine: Metoclopramide may increase serum prolactin concentrations and interfere with effects of bromocriptine thus necessitating a dosage adjustment of the bromocriptine.
5. Other CNS depression producing drugs; concurrent use may potentiate the sedative effects of either these drugs or the metoclopramide.
6. Extrapyramidal reaction causing drugs (such as phenothiazines and tetrabenazine): Concurrent use with metoclopramide may increase the frequency and severity of extrapyramidal side effects. Care should be exercised in the event of co-administration of these drugs
7. Levodopa: Concurrent use with metoclopramide may accelerate gastric emptying of levodopa, thus possibly increasing its rate and extent of absorption from the small intestine; the clinical significance of metoclopramide induced changes in the absorption of drugs primarily absorbed in the small intestine has not been determined.
8. Metoclopramide should be used with care in association with other drugs acting at central dopamine receptors, such as pergolide.
9. Mexiletine: Concurrent use with metoclopramide may accelerate absorption of mexiletine.
10. Diagnostic interference: With Gonaderelin test, concurrent use with metoclopramide may blunt the response to gonaderelin by increasing serum prolactin concentrations. Concurrent metoclopramide therapy may increase aldosterone and serum prolactin levels.
11. The absorption of any concurrently administered oral drug may be modified by the effect of metoclopramide on gastric motility. Drugs known to be affected in this way include aspirin and paracetamol.
12. Metoclopramide may reduce plasma concentrations of atovaquone
4.6 Pregnancy And Lactation
Although extensive studies in humans have not been done, animal tests in several mammalian species have not indicated a teratogenic effect. None the less, metoclopramide should only be used if there are compelling reasons, and it is not advised during the first trimester,
In breast feeding, problems in humans have not been documented; however risk-benefit must be considered as metoclopramide is excreted in the breast milk.
4.7 Effects On Ability To Drive And Use Machines
This preparation may cause drowsiness. If affected patients should avoid driving or using machinery.
4.8 Undesirable Effects
For symptoms of overdose, see Overdose.
Various extrapyramidal reactions to metoclopramide, usually of the dystonic kind, have been reported. Incidence of dystonic reactions, particularly in children and young adults, is increased if daily doses in excess of 0.5mg/kg body weight are used. Examples of dystonic reactions include: facial muscle spasm, trismus, bulbar type speech, rhythmic tongue protrusion, spasm of extra-ocular muscles (including oculogyric crises), unnatural positioning of head and shoulders and opisthotonos. There may also be a generalised increase in muscle tone. In most cases, the majority of these reactions occur within 36 hours of initiating treatment, they usually reverse within 24 hours of drug withdrawal. If necessary, dystonic reactions may be treated by use of an anticholinergic anti-parkinsonian drug, or a benzodiazepine. Tardive dyskinesia, occurring during prolonged treatment, has been reported, mainly in elderly patients; such patients should be regularly reviewed.
Very rare occurrences of neuroleptic malignant syndrome have been reported. This syndrome is potentially fatal and comprises of hyperpyrexia, altered consciousness, muscle rigidity, autonomic instability and elevated levels of creatinine phosphokinase (CPK) and must be treated urgently (recognised treatments include dantrolene and bromocriptine). Metoclopramide should be stopped immediately if this syndrome occurs.
Other side effects and approximate incidence:-
Drowsiness (about 10%), restlessness (about 5%), unusual tiredness or weakness (about 10%).
The following are less frequent or rare:
Breast tenderness and swelling, constipation (less than 1%), changes in menstruation, depression, diarrhoea, dizziness (less than 1%), headache, nausea, skin rash, trouble sleeping, unusual dryness of mouth, unusual irritability and confusion. Depression has been reported extremely rarely
Raised serum prolactin levels have been observed during metoclopramide therapy: this may result in galactorrhoea, irregular periods and gynaecomastia.
Extremely rarely cases of red cell disorders such as methaemoglobinaemia and sulphaemoglobinaemia have been reported, particularly at high doses of metoclopramide. If this occurs the drug should be withdrawn. Methaemoglobinaemia may be treated using methylene blue
A small number of skin reactions such as urticaria, pruritus and oedema (including face oedema). Allergic reactions may also occur. Very rarely hypersensitivity, including anaphylaxis has been reported.
4.9 Overdose
1. Symptoms of overdose
Confusion, severe drowsiness, muscle spasms, especially of jaw, neck, back, shuffling walk, tic like (jerky) movements of head and face, trembling and shaking of hands (extrapyramidal effects).
2. Treatment
Gastric lavage and appropriate supportive measures. For treatment of dystonic reactions, see under undesirable effects.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Metoclopramide is a dopaminergic blocker, acting as a delayed gastro-intestinal emptying adjunct and as a peristaltic stimulant. The exact mechanism of action is unknown; it is believed that metoclopramide inhibits gastric smooth muscle relaxation produced by dopamine thus enhancing cholinergic responses of the gastrointestinal smooth muscles. Accelerates intestinal transit and gastric emptying by preventing relaxation of gastric body and increasing the phasic activity of antrum. At the same time, this action is accompanied by relaxation of the upper small intestine, resulting in an improved co-ordination between the body and the antrum of the stomach and the upper small intestine. Decreases reflux into the oesophagus by increasing the resting pressure of the lower oesophageal sphincter and improves acid clearance from the oesophagus by increasing amplitude of oesophageal peristaltic contractions.
As an anti-emetic; the dopamine antagonist action raises the threshold of activity in the chemoreceptor trigger zone and decreases the input from afferent visceral nerves.
Metoclopramide also stimulates prolactin secretion.
5.2 Pharmacokinetic Properties
Animal studies have shown metoclopramide to bind to plasma protein (13% - 22%), especially plasma albumin.
Biotransformation is by the hepatic route.
Metoclopramide has a half life of four to six hours. The onset of action, by oral route of administration, is from 30 to 60 minutes.
The duration of action is 1 to 2 hours.
Elimination is by the renal route, approximately 85% of an oral dose appears in the urine as unchanged drug and as sulphate and glucuronide conjugates.
5.3 Preclinical Safety Data
None stated
6. Pharmaceutical Particulars
6.1 List Of Excipients
Methyl hydroxybenzoate, propyl hydroxybenzoate, propylene glycol, sorbitol solution 70%, glycerin, citric acid monohydrate, lime and lemon flavours, sodium citrate and purified water.
6.2 Incompatibilities
Not applicable
6.3 Shelf Life
24 months
6.4 Special Precautions For Storage
Store below 25°C and protect from light.
6.5 Nature And Contents Of Container
Bottles: Amber Type III glass bottles
Capacities 30ml, 100ml, 150ml, 200ml, 500ml, 1000ml
Closures:
a) Aluminium , EPE wadded, roll-on pilfer proof
b) HDPE, EPE wadded, tamper evident
c) HDPE, EPE wadded, tamper evident, child resistant
6.6 Special Precautions For Disposal And Other Handling
Keep out of the reach of children.
7. Marketing Authorisation Holder
Rosemont Pharmaceuticals Ltd
Rosemont House
Yorkdale Industrial Park
Braithwaite Street
Leeds
LS11 9XE UK
8. Marketing Authorisation Number(S)
00427/0117
9. Date Of First Authorisation/Renewal Of The Authorisation
1 July 1998
10. Date Of Revision Of The Text
27 November 2007
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